Available online on 15.09.2021 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2021 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access  Full Text Article                                                                                                                                           Review Article 

Laurus nobilis L., (Habb-ul-Ghar), A Review on Phytochemistry, Pharmacology and Ethnomedicinal Uses

Qamrul Islam Usmani , Altaf Ahmad* , Fathima Nairoza Jamaldeen                       

Dept. of Ilmul Advia (Pharmacology), National Institute of Unani Medicine, Kottigepalaya, Magadi Main Road, Bengaluru-91, India

INTRODUCTION

As the name implies, the Unani system of medicine has its roots in ancient Greece and has been further refined by Roman, Arabic, Spanish, Iranian, and Indian physicians. As a result, Greco-Arab Medicine was born. It is a holistic medical system that systematically addresses various health and illness conditions. It involves healthcare that is preventive, curative, and rehabilitative. According to the Unani concept, the human body comprises seven basic components: element, temperament, humour, organ, pneuma, faculties, and functions. The mere absence of any components directly impacts life's very existence, and its imbalance leads to disease. The Medicatrix Naturae (Ṭabī‘at mudabbira-i-badan), according to the Unani system of medicine, is the supreme power that regulates all physiological functions of the body, gives resistance to diseases, and promotes natural healing. The system's foundations, diagnostic, and treatment techniques are based on scientific principles and holistic health and healing theories. Rather than taking a reductionist view of sickness, it uses a holistic approach that considers the entire individual¹.

Laurus nobilis L., commonly known as laurel or sweet bay, is a perennial shrub or tree, a native of the Mediterranean countries, widespread in temperate and warm regions². In Unani system of medicine, its fruit is used with the name of Habb-ul-Ghar³. Fareed Ahmad Abbasi mentioned in Saidla Al-Jameela that Asqaliboos Awwal (Asklepiades, 1^st Century) has started preparation of Tiryaq (antidote) from single ingredient Habb-ul-Ghar. Later, Unani physician Indru Makhiz added four ingredients and give the name ‘Tiryaq Arba’⁴. The popularity of Tiryaq Arba is growing in the current epidemic situation, where it can be used as a preventative medicine⁵. It is widely cultivated in Europe, America, Western Asia, Northern Africa, Arabian countries, and   India^6,7. The essential oil can be extracted from the plant leaves and fruits, while fixed oil derived mainly from the berries. Bay laurel essential oil has been discovered to have a variety of remarkable qualities that have a wide range of potential applications in various fields, including seafood, meat preservation, veterinary, and cosmetics, as well as health⁸. The usage of laurel in cuisines has become more widespread in recent years, with its notably fragrant leaves and berries being used in various culinary preparations⁹. Moreover, the fruits and leaves of L. nobilis have been used in traditional medicine for rheumatism, dermatitis, viral infections, antiseptic, hysteria, emmenagogue, diuretic, general gastric secretion stimulant, carminative, diarrhoea, and antidote in snake bites since antiquity^6,10–12.

MATERIAL AND METHODS

Habb-ul-ghar was explored in classical Unani literature for its temperament (mizaj), medicinal properties and therapeutic uses. Urdu translation of the classical books such as Al Jami ul Mufradat Al Advia Wal Aghzia of Ibn al Baitar (1197-1248 AD), Muheet Azam of Hakeem Mohammad Azam Khan (1806–1902 AD), Khazainul Advia of Najmul Ghani, (19th century), Al Mukhtarat fit Tib of Ibn Hubl Baghdadi (1122 -1213 AD), and Tazkira Oolul Albab (Arabic) of Dawud al Antaki (1541-1599 AD), Tuhfat ul Momineen (Persian) of Momin Tonekaboni (1669 AD), etc., were conferred. Published works available on PubMed, Science Direct, and Google Scholar were referred to collect all the available information regarding its phytochemicals and pharmacological studies. Standard Unani Medical Terminology published by Central Council for Research in Unani Medicine in collaboration with the World Health Organization was used to describe the appropriate Unani terminologies.

DESCRIPTION OF HABB-UL-GHAR IN UNANI LITERATURE

Table 1: Common name in a different region

Morphology (Māhiyat): Habb-ul-ghar is the fruit of a large tree that lives long nearly one thousand years^16,17. It is smaller than Funduq (fruit of Sapindus trifoliatus) but similar to the fruit of Neem (Melia azaderachta). Leaves resemble Barg Aas (leaves of Myrtus communis), giving a particular fragrance on mashing like Badam Talkh (Prunus amygdalus)^3,18. The peel of the fruit is off-white blackish but very thin and fragile. Fruit divide into two parts on rubbing between two fingers. The seeds are hard, shiny, smooth surface, orange in colour, and possess a slight fragrance^3,19. The fruits are bitter but fragrant^20,21. Berries and bark are used alone or as an ingredient of compound formulations in the Unani system of medicine. It is mainly found in Asia Minor and Europe. In India, it was trying to be cultivated on Nilgiris hills but unable to grow properly, so it is imported from abroad²².

Parts used (Hasas-i-Musta’mla): In Unani system of medicine mostly fruits and essential oil are used,^{3,16,19–21,23} but leaves and other parts are used in other traditional systems of medicine^{6,13,14,24,25}.

Temperament (Mizāj):  The temperament of drugs has remained key to the theory of drug action in the Unani system of medicine, and it is one of the basic fundamental concepts. The temperament of a person and the drug's temperament serves as a conceptual framework for adequately using the medicine, predicting its effect on the body, and serving as an indicator of drug potency. Unani physicians have divided the drugs into four categories (hot, cold, wet, and dry) in terms of their effect on a moderate human body. The temperament of Habb-ul-Ghar is hot and dry in the second degree^18,21,22; Hot and Dry in third-degree^17,26.

Action and uses (Af ̒ āl aur Mawāq-i-istemāl)

It has several pharmacological properties such as Muḥallil-i-awrām (resolvent: a substance that dissolves thick and viscous humour, hence reducing inflammation and swelling), Musakkin-i-alam (analgesic: an agent which relieves the pain), Muḥarrik-i-a‘sāb (nervine stimulant: an agent which stimulates the nerves). Mufarriḥ (refrigerant: a drug that reduces tachycardia, palpitation of heart and thirst), Muqawwi (tonics: a non-toxic natural substance that tone up the internal organs and improve the body functions), Musakkin (sedative: a substance which helps in neutralizing the heat of humour), Muqaww-i-bāh (aphrodisiac: an agent which strengthens the sexual organs and boosts the libido), Muqawwi-i-Mi‘da (stomachic: an agent which strengthens the stomach and improves its function), Kasir-i-riyaḥ (carminative: a substance that promotes to release gases from the gastrointestinal tract)^17,18,21,23.

• Habb-ul-gar is an important antidote for all poisons and is used internally or externally with wine for snake bites, scorpions, and other insect bites^3,19,22,23. 
• Habb-ul-ghar used alone or in conjunction with honey is effective in phlegmatic headache, flatulence, epilepsy, duodenal ulcer, and strengthens Quwwat ḥāfiẓa (faculty of memory)^3,19–21.
• 9 g powdered Habb-ul-ghar when ingested orally found effective in numbness, paralysis, and facial palsy^3,19,20.
• When used as ear drops, the ground Habb-ul-ghar in Roghan Gul or vinegar relieves tinnitus, deafness, and otalgia^3,16,19,21. 
• Gargling with the decoction of Habb-ul-ghar relieves toothache^16,22.
• Habb-ul-ghar as linctus, mixed with honey and taken orally, is effectively used in dyspnoea, lung ulcer, chronic cough, and phlegmatic disease of the chest^3,19,20,23.
• Habb-ul-ghar 7 g taken with Sikanjabīn or honey expel viscous humours and act as purgative^19,20,23. Moreover, it dissolves the viscous gases and is also helpful in Maghṣ (tenesmus), Qūlanj (colic), liver and spleen disorder. In another regimen, 9 g Habb-ul-gahr powder taken with the mucilage of Isapghol gives instant relief in intestinal colic^19,20,22.
• 4.5-9 g Habb-ul-ghar mixed with wine when given orally relieves incontinence and dribbling of micturition, helps in parturition, and also acts as an emmenagogue^3,18,19,23.
• 3.5 g of Habb-ul-ghar, when taken orally with water, shows a lithotriptic effect^3,16,19,23.
• In conjunction with Sikanjabeen (a liquid preparation made with vinegar and honey/sugar), Habb-ul-gar was found effective in a disease of hot temperament and, when taken with honey, gives a beneficial result in conditions of cold temperament, as advised by Dawud Antaki. He also advised to use as Naṭul (irrigation) for resolvent; Ābzan (sitz bath) for rectal and uterine diseases; Firzaja (pessary) for abortion and diuretics²⁰.
• Roghan (oil) of Habb-ul-ghar used tropically in Dā’al-tha‘lab (alopecia areata), Qūbā (ringworm), Qatil-i-qaml (kills the lice), Waja‘ al-Mafāsil (polyarthritis), Niqris (gout), Waja‘ al-Ẓahr (backache), Jarab wa Ḥikka (scabies and pruritis), Fālij (hemiplegia), Laqwa (facial palsy), Waja‘ al-kabid (hepatic pain), Waja‘ al-āsāb (neuralgia), strengthening of muscle and found very effective.³ It is concoctive to Awram balghamiya (phlegmatic inflammation) and Muḥallil-i riyaḥ (resolve flatus)²⁷.

Dose (Miqdār-i-khorāk): The dose of Habb-ul-ghar is 2-3 gm and up to 9 gm for purgation purposes^3,17,19.

Adverse effects (Muzir): According to Ibn Sina, Habb-ul-ghar induces Qay’ (vomiting); muscle and ligament of the stomach become flaccid i.e. Istirkha’ al-mi‘da (gastroptosis)^3,19,22. It is also harmful to the liver^17,26.

Correctives (Musleḥ): Zarishk (Berberis vulgaris),^3,17,19; Katira (Sterculia urens);²¹ Tabasheer (Bambusa arundinacea)²⁶ 

Substitute (Badal): Haab-ul-Mahlab (Prunus mahaleb), Badam Talkh (Prunus amygdalus);^3,19 Shooneez (Nigella sativa)^17,26; Sazaj (Cinnamomum tamala)²⁰

Unani formulation 

Table 2: Showing compound formulations of Habb-ul-ghar, dosage and indications

Habb-ul-Ghar (Laurel fruit) in other Traditional medicine

In Iran, a decoction of dried fruit is taken orally as an appetite stimulant & digestive aid. In Israel, fruit essential oil is used externally on wounds, rheumatic & neuralgic pain. The dried fruit in hot water extract orally as a circulatory stimulant and externally to soften tumours and ulcers in Peru. Fruits are taken in Europe orally during childbirth to speed up delivery.¹⁴ In India, fruit is taken orally as an emmenagogue, anti-leucorrhea, and anti-diarrheal.⁶ The dried macerated fruit with Olive oil is used as antirheumatic in Italy.¹⁴ The fruit has stimulant and narcotic properties, used for hysteria, amenorrhea, and flatulent colic; yield an aromatic fat, applied as a stimulant in sprains.²⁵ The aqueous extract of the L. nobilis fruits has been used in Turkish folk medicine as an anti-hemorrhoidal, antirheumatic, antidote in snakebites, and stomach ache¹².

DESCRIPTION OF HABB-UL-GHAR IN THE SCIENTIFIC LITERATURE

Taxonomical classification:  kingdom: Plantae; Division: Magnoliopsida; Order: Laurels; Family: Lauraceae; Genus: Laurus; Species: nobilis³¹

Plant description: Laurus nobilis L. is a profusely branched shrub or a small size tree, usually grow up to height of 10 meters.

Figure 1(a): Laurus nobilis Plant                                              Figure 1(b): Laurus nobilis Fruit

Source: (a) https://i.pinimg.com/originals/e3/ad/77/e3ad772b24230e9fe3902ca974673925.jpg 

               (b) https://2.bp.blogspot.com/ePiqmmezjeE/VtRzCBfNSDI/AAAAAAAHmY/7k7_Saihugg/s1600/64253_1.

Table 3: Botanical description of Laurus nobilis L.^7,14,32

Microscopic feature of fruit: On sectional view, the testa shows the epidermis made up of rectangular to squarish parenchymatous cells coated with cuticle on the outer surface and most of these cells found to possess yellowish-brown contents which give test for protein. Polygonal to oval parenchymatous cells and numerous oil cells make up the several layered zones under the epidermis. The oil containing cells are oval to round, large and with slightly thickened wall. The innermost surface of testa is attached to endosperm. In endosperm, there is a single layer of radially elongated highly thick-walled cells. The parenchymatous cells of the endosperm are found highly thick-walled cells and containing yellowish brown mass. The epidermis of the cotyledon is single layered, and the cells are small, rectangular to squarish in shape and outer walls of the cells are thickened. Ground tissue is mostly composed of thin walled polygonal to oval parenchymatous cells; the cells possess numerous aleurone grains which are simple and oval to round³³.

PHYTOCHEMISTRY

The main bioactive compounds of Habb-ul-ghar (Laurel fruit) with a focus on their isolation and identification are listed in Table 4. Laurus nobilis fruits contained organic compounds viz. phenolics, steroids, glycoside, fixed and essential oil, tannins, resins, flavonoids, carbohydrates, proteins and iron, calcium, sodium, potassium, etc. phosphate as inorganic compounds³³.

Table 4: The main secondary metabolites identified from L. nobilis (fruit)

PHARMACOLOGICAL STUDIES

Figure 2: Pharmacological studies of L. nobilis fruit

Anti-ulcer activity: Crude aqueous extracts of 20 and 40% and an oily solution of the seeds of L. nobilis were evaluated for anti-ulcer activity. The results revealed that the crude extract and the volatile oil fraction had a gastroprotective effect with the dose of 1 ml/100 g body weight when ulcer was induced at 0.5 ml/100 g ethanol as an ulcerogenic agent. The 40% extract was able to exhibit gastroprotective action when the amount of ethanol was increased to 1 ml/100 g⁴⁴.

Antioxidant activity: The antioxidant activities of different extracts of L. nobilis fruit (pericarp and kernel) were performed by a DPPH assay and a β-carotene-linoleic acid assay. In the DPPH method, the highest activity (29.43%) was observed in the pericarp extract from maceration with 80% ethanol at the level of 12 µg/ml. Kernel extract obtained by Soxhlet extraction with 80% ethanol showed the most potential activity (50.78%) at the concentration of 12 µg/ml. In the β-carotene-linoleic acid method, pericarp extract of 50% methanol exhibited the strongest neutralising activity (85.56%) of free radicals, and the highest activity was observed in the kernel extract (69.93%) obtained by kinetic extraction with 80% ethanol⁴⁵.

Antioxidative activity of Laurus nobilis fruit methanolic extract (crude and defatted) was studied on the level of lipid peroxidation in liposomes induced by the Fe²⁺/ascorbate system and measured spectrophotometrically by the TBA-test. The significant inhibition of lipid peroxidation was obtained after applying 2.0 mg crude methanolic extract of laurel fruit¹¹.

Ozcon (2010) also evaluated the antioxidant activity of the essential oil and methanolic extract of seed oil from L. nobilis by employing two complementary tests, namely DPPH free radical scavenging and β-carotene/linoleic acid test. This study shows the antioxidant property of the methanolic extract of the seed oil is higher than the essential oil obtained from laurel fruits, and methyl eugenol may be considered the main contributor to this activity⁴⁶.

In another study, the essential oil from the seed of laurel fruits exhibited a scavenging effect on the DPPH radical, with IC₅₀ values of 66.1±1.8 μg/ml and inhibited oxidation of linoleic acid after 30 as well as 60 min of incubation with IC₅₀ of 41.1±1.2 and 45.9±1.3 μg/ml. The result was found significant (p˂0.01) compared to ascorbic acid and propyl gallate as standard control⁴⁷.

Antiproliferative activity: Abu-Dahab et al. (2014) evaluated the antiproliferative activity of ethanol extract of the fruits on human breast adenocarcinoma (MCF7) and human ductal carcinoma (T47D), which exhibited prominent antiproliferative activity with an IC₅₀ of 12.3 µg/mL for T47D cell line and 28 µg/mL for MCF7 cells. The antiproliferative activity of the extracts is attributed to the flavonoids and sesquiterpenes present in the laurel fruits⁴⁸.

Essential oil of L. nobilis fruit has exerted antiproliferative activity against K562 cells with IC₅₀ values of 75 μg/ml. The seed oil showed a 12% erythroid differentiation at the concentration of 50 μg/ml. The result showed that seeds essential oils can inhibit the in vitro proliferation of K562 cells⁴⁷.

In another study, cytotoxicity was determined against A2780 human ovarian cancer cells using a microtiter plate assay, and actinomycin D was used as a positive control. The crude methanol extracts of fruits of L. nobilis showed the highest activity with 98% inhibition. The sesquiterpenes costunolide and zaluzanin D, which are present in the laurel fruits, are considered to be responsible for the observed cytotoxicity²⁴.

Antimicrobial activity: The antimicrobial activity of ethanolic crude extracts of L. nobilis fruit was evaluated against four Gram-positive bacteria (Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus subtilis, and Bacillus cereus), five Gram-negative bacteria (Escherichia coli, Klebsiella pneumonia, Salmonella typhimurium, and Chromobacterium violaceum Pseudomonas aeruginosa); four fungal species was included viz. Aspergillus fumigatus, Aspergillus niger, Candida albicans, and Candida glabrata using the agar diffusion method. The result showed a moderate zone of inhibition against all bacteria and fungi. Also, an anti-quorum sensing assay was done at the concentration of 3 mg per disc. Chromobacterium violaceum quorum sensing system was used for this test, and Tetracycline was used as a positive control. The quorum sensing zone of inhibition was observed 15±0.9 for the laurel fruit⁴⁹.

In another study, methanolic extract of seed oil showed significant antimicrobial activity against Gram-positive bacteria viz. S. aureus, methicillin-resistant S. aureus, B. subtilis, E. gallinarium, L. monocytogenes, and one Gram-negative bacteria, H. influenza, on agar well diffusion method⁴⁶.

The antimicrobial activity of fatty oil from L. nobilis fruit was evaluated with minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) by a microtiter broth dilution method against S. epidermidis, E. faecalis, P. aeruginosa, S. aureus, and E. coli. The result showed that fatty oil has good antibacterial activities⁵⁰.

Antimicrobial activity of essential oil from L. nobilis fruits from Greece and Georgia was evaluated by agar disk diffusion and the broth microdilution method. The effects of both EOs on Bacillus cereus, Staphylococcus aureus, Escherichia coli, Salmonella abony, Pseudomonas aeruginosa, Pseudomonas fluorescens and the dimorphic yeast Candida albicans were evaluated. The result demonstrated low to moderate antimicrobial activity compared with the positive controls (Ciprofloxacin and Fluconazole) against all test microorganisms except Pseudomonas species¹⁰.

Antinociceptive activity: In vivo, antinociceptive activity was carried out by 2.5% (w/v) p-Benzoquinone-induced writhing test in male Swiss albino mice (20-25 g) at the doses 0.1 mL/10 g of body weight. The Aspirin at 100 and 200 mg/kg doses was used as a reference drug. The ethanolic and aqueous extract of L. nobilis seed suspended in CMC was given orally in two doses, 250 and 500 mg/kg, 60 minutes before the induction. The number of writhes with ethanolic extract was found 35±3.3 with an inhibitory ratio of 34% at the dose of 500 mg/kg. The result demonstrated a statistically significant (P˂0.01) antinociceptive effect⁵¹.

Anti-inflammatory activity: The aqueous and ethanolic extract of the L. nobilis seed was evaluated by carrageenan (0.5 mg/25 mL) induced hind paw oedema on the male Swiss albino mice. Indomethacin (10 mg/kg of body weight) was used as standard control. The ethanolic extract of L. nobilis seed at 500 mg/kg doses exhibited significant (P˂0.001) anti-inflammatory activity.⁵¹ In another in vivo anti-inflammatory study, fixed oil from the Laurus nobilis fruit exhibit oedema with 26.33% of inhibition and found significant (p <0.05) results as compared to the Diclofenac standard drug. The fruits consist of flavonoids and saponins, which may be at the origin of their anti-inflammatory properties⁵².

Antiviral activity:

L. nobilis fruit essential oil has been evaluated for their inhibitory activity against SARS-CoV and HSV-1 replication in vitro by visually scoring of the virus-induced cytopathogenic effect post-infection. The results demonstrated that fruit oil exhibited an IC₅₀ value of 120 mg/ml against SARS-CoV with a selectivity index (SI; TC₅₀/IC₅₀) of 4.2. An interesting activity with an IC₅₀ value of 60 mg/ml was found when fruit oil was incubated with HSV-1 virus³⁵.

Clinical trial: A Single-blind randomised standard controlled study for the primary dysmenorrhoea was conducted at NIUM Hospital, Bengaluru. Habb ul Ghar powder 4.5g was used to make a pill, and 2 pills TID with 20 ml Maul Asal was given to the patients for five days. Mefenamic acid 500 mg BD was used as a standard drug. The results were analysed based on visual analogue scale (VAS) and verbal multidimensional scoring system (VMSS), which was enormously significant (p<0.001) and almost equivalent to the standard control⁵³.

CONCLUSION                                                                                

Laurus nobilis L., a plant of Lauraceae family, has been mentioned in the Unani system of medicine as Habb-ul-Ghar. There are several phytoconstituents in Laurus fruit that are significant components in the plant's medicinal effectiveness. Many studies have found its strong anti-inflammatory, antimicrobial, antiproliferative, anti-oxidant properties. A comprehensive research and development effort should be made to develop products for better economic and therapeutic use. Also, more clinical trials are needed to validate the therapeutic efficacy of this Unani drug.

Declaration of competing interest

There is no conflict of interest.

ACKNOWLEDGMENT

The authors are highly obliged to the Director and Librarian, NIUM, Bangalore, to provide facilities in the library to review the literature regarding the topic. Furthermore, authors are thankful to the authors, editors, and publishers of all those books and journals from where the literature of this article has been reviewed.

REFERENCES

1. Usmani QI, Jahan N, Aleem M, Hasan SA. Aatrilal (Ammi majus L.), an important drug of Unani system of medicine: A review. J Ethnopharmacol. 2021; 276(12):114-144. Available from: https://doi.org/10.1016/j.jep.2021.114144

2. Prajapati ND, Purohit SS, Sharma AK. A Hand book of Medicinal Plants. Jodhpur: Agrobios (India); 2009; 308.

3. Ghani N. Khazain ul Advia (Musawwir edition) Vol. I-IV. 3rd ed. New Delhi: Idara kitab us-shifa; 2011; 645, 957-58.

4. Rafeequddin M. Minhaj us Saidla wal Kimia. New Delhi: Idara kitab us-shifa; 2001; 40.

5. Ansari S, Ahmad I, Ali M, Maaz M. "Tiryaq arba" (a polyherbal Unani formulation) as prophylactic medicine against epidemics of acute respiratory viral infections. Middle East J Rehabil Heal Stud. 2020; 7(3):1-10. https://doi.org/10.5812/mejrh.102965

6. Khare CP. Indian Medicinal Plant, An illustrated Dictionary. New Delhi: Springer India Private limited; 2007; 43. https://doi.org/10.1007/978-0-387-70638-2

7. Batool S, Khera RA, Hanif MA, Ayub MA. Bay Leaf. 2020; 63-74. https://doi.org/10.1016/B978-0-08-102659-5.00005-7

8. Yilmaz B, Deniz I. The Effects of Cultivation Area and Altitude Variation on the Composition of Fatty acids of Laurus nobilis L. berries in Nothern Turkey and Abkhazia. Eurasian J For Sci. 2018; 6(4):14-21. https://doi.org/10.31195/ejejfs.460501

9. Ovidi E, Zambelli M, Tiezzi A. Laurus nobilis, Salvia sclarea and Salvia officinalis Essential Oils and Hydrolates: Evaluation of Liquid and Vapor Phase Chemical Composition and Biological Activities. Plants. 2021; 10(707):1-17. https://doi.org/10.3390/plants10040707

10. Petkova Z, Stefanova G, Girova T, Antova G, Stoyanova M, Damianova S, et al. Phytochemical Investigations of Laurel Fruits (Laurus nobilis). Nat Prod Commun. 2019; 14(8):1-10. https://doi.org/10.1177/1934578X19868876

11. Simic M, Kundakovic T, Kovačevic N. Preliminary assay on the antioxidative activity of Laurus nobilis extracts. Fitoterapia. 2003; 74(6):613-6. https://doi.org/10.1016/S0367-326X(03)00143-6

12. Yahyaa M, Berim A, Isaacson T, Marzouk S, Bar E, Davidovich-Rikanati R, et al. Isolation and Functional Characterization of Carotenoid Cleavage Dioxygenase-1 from Laurus nobilis L. (Bay Laurel) Fruits. J Agric Food Chem. 2015; 63(37):8275-82. https://doi.org/10.1021/acs.jafc.5b02941

13. Nadkarni KM. Indian Materia Medica, Vol I. 3rd ed. Mumbai: Popular Prakashan Limited; 2009; 729.

14. Ross IA. Medicinal Plants of the World:Chemical Constituents, Traditional and Modern Uses, Vol. II. Totowa, NJ: Humana Press Inc.; 2001; 261-70.

15. Ibn al Baitar. Al-Jam-e-ul-Mufradat-Al-Adviah-Wal-Aghziya (Urdu translation, Vol. IV. New Delhi: Central Council of Research in Unani Medicine (CCRUM); 2003; 327-29.

16. Momin Tonekaboni M. Tohfat ul Momineen (Persian). Matba Hasni; 1855; 181.

17. Nabi GM. Makhzan ul Mufredat wa Murakkabat maroof ba Khwasul Advia. 2nd ed. New Delhi: CCRUM; 2007; 171.

18. Kabeeruddin M. Makhzan ul Mufredat. 3rd ed. New Delhi: Idara kitab us-shifa; 2014; 298.

19. Khan M. Muheet e Azam (urdu translation) Vol. II. New Delhi: CCRUM Publication; 2018; 304-05.

20. Antaki D. Tazkira Ulul Albab Wal Jamia Lil Ajbul Ijab (Arabic). 2nd ed. New Delhi: CCRUM; 2008; 457-58.

21. Abdul Hakeem M. Bustan Al-Mufradat Jadid. New Delhi: Idara kitab us-shifa; 2002; 399.

22. Rafeequddin M. Kanzul Advia Mufredat. Aligarh: University Publication Unit, AMU; 1985; 294-95.

23. Baghdadi IH. Al Mukhtarat Fit Tib (Urdu Translation), Vol. II. New Delhi: Central Council of Research in Unani Medicine (CCRUM); 2005; 109, 296.

24. Barla A, Topçu G, Öksüz S, Tümen G, Kingston DGI. Identification of cytotoxic sesquiterpenes from Laurus nobilis L. Food Chem. 2007; 104(4):1478-84. https://doi.org/10.1016/j.foodchem.2007.02.019

25. Anonymous. The Useful Plants of India (5th Reprint). New Delhi: National Institute of Science Communication and Information Resources; 2006; 319.

26. Ibrahim Maghribi AS. Kitab ul Fatah fit Tadava. New Delhi: Central Council of Research in Unani Medicine (CCRUM); 2007; 234-35.

27. Maseehi AAIQ. Kitabul Umda fil Jarahat (Urdu translation by CCRUM) Vol II. New Delhi: Central Council of Research in Unani Medicine (CCRUM); 2000; 282.

28. Arzani A. Qarabadeen Qadri. New Delhi: Aijaz publishing house; 1998; 511.

29. Anonymous. Qarabadeen Majeedi, 9th ed. New Delhi: Hamdard Dawakhana (Waqf); 1986; 36.

30. Anonymous. National Formulary of Unani Medicine, Part I, Vol. II-III. New Delhi: Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH) Government of India; 2007.

31. Patrakar R, Mansuriya M, Patil P. Pharmacological Review on Laurus nobilis. Int J Pharm Chem Sci. 2012; 1(2):595-602.

32. Wallis TE. Text Book of Pharmacognosy, 5th ed. New Delhi: CBS Publishers and Distributors; 2005; 264.

33. Anonymous. Standardisation of single drugs of Unani medicine - Part V. New Delhi: CCRUM Publication; 2006; 89-92.

34. Fidan H, Stefanova G, Kostova I, Stankov S, Damyanova S, Stoyanova A, et al. Chemical Composition and Antimicrobial Activity of Laurus nobilis L. Essential oils from Bulgaria. Molecules. 2019; 24(4):1-10. https://doi.org/10.3390/molecules24040804

35. Loizzo MR, Saab AM, Tundis R, Statti GA, Menichimi F, Lampronti D, et al. Phytochemical analysis and in vitro antiviral activities of the essential oils of seven Lebanon species. Chem Biodivers. 2008; 5(3):461-70. https://doi.org/10.1002/cbdv.200890045

36. Said, CM and Hussein K. Determination of the chemical and genetic differences of Laurus collected from three different geographic and climatic areas in Lebanon. In: European Scientific Journal. 2014: 412-9.

37. Sangun MK, Aydin E, Timur M, Karadeniz H, Caliskan M, Ozkan A. Comparison of chemical composition of the essential oil of Laurus nobilis L. leaves and fruits from different regions of Hatay, Turkey. J Environ Biol. 2007; 28(4):731-3.

38. Elkiran O, Akbaba E, Bagci E. Constituents of essential oils from leaves and seeds of Laurus nobilis L.: A chemotaxonomic approach. Bangladesh J Bot. 2018; 47(4):893-901. https://doi.org/10.3329/bjb.v47i4.47379

39. Zolfaghari B, Samsam-Shariat SH, Ghannadi A. Chemical composition of volatile oils from the endocarp and hulls of persian bay laurel fruit: A fragrant herb used in traditional Iranian medicine. J Reports Pharm Sci. 2013;2(1):1-4.

40. Kilic A, Hafizoglu H, Kollmannsberger H, Nitz S. Volatile Constituents and Key Odorants in Leaves, Buds, Flowers, and Fruits of Laurus nobilis L. J Agric Food Chem. 2004; 52(6):1601-6. https://doi.org/10.1021/jf0306237

41. Appendino G, Tagliapietra S, Mario Nano G, Cisero M. A sesquiterpene alcohol from the fruits of Laurus nobilis. Phytochemistry. 1992; 31(7):2537-8. https://doi.org/10.1016/0031-9422(92)83320-X

42. Longo L, Vasapollo G. Anthocyanins from bay (Laurus nobilis L.) berries. J Agric Food Chem. 2005; 53(20):8063-7. https://doi.org/10.1021/jf051400e

43. Ramadan AZ, Mandil HAL. Effect of Ripening Time of Fruits in the Chemical Composition (%) of Fatty Acids in Syrian Laurel Oil. Int J Curr Res Chem Pharm Sci. 2019; 6(7):27-32. Available from: https://doi.org/10.22192/ijcrcps.2019.06.07.004

44. Afifi FU, Khalil E, Tamimi SO, Disi A. Evaluation of the gastroprotective effect of Laurus nobilis seeds on ethanol induced gastric ulcer in rats. J Ethnopharmacol. 1997; 58(1):9-14. https://doi.org/10.1016/S0378-8741(97)00070-6

45. Bozan B, Karakaplan U. Antioxidants from laurel (Laurus nobilis L.) berries: Influence of extraction procedure on yield and antioxidant activity of extracts. Acta Aliment. 2007; 36(3):321-8. https://doi.org/10.1556/AAlim.36.2007.3.4

46. Ozcan B, Esen M, Kemal Sangun M, Coleri A, Caliskan M. Effective antibacterial and antioxidant properties of methanolic extract of Laurus nobilis seed oil. J Environ Biol. 2010; 31(5):637-41.

47. Saab AM, Tundis R, Loizzo MR, Lampronti I, Borgatti M, Gambari R, et al. Antioxidant and antiproliferative activity of Laurus nobilis L. (Lauraceae) leaves and seeds essential oils against K562 human chronic myelogenous leukaemia cells. Nat Prod Res. 2012; 26(18):1741-5. https://doi.org/10.1080/14786419.2011.608674

48. Abu-Dahab R, Kasabri V, Afifi FU. Evaluation of the volatile oil composition and antiproliferative activity of Laurus nobilis L. (Lauraceae) on breast cancer cell line models. Rec Nat Prod. 2014; 8(2):136-47.

49. Al-Hussaini R, Mahasneh AM. Microbial growth and quorum sensing antagonist activities of herbal plants extracts. Molecules. 2009; 14(9):3425-35. https://doi.org/10.3390/molecules14093425

50. Chmit M, Kanaan H, Habib J, Abbass M, Mcheik A, Chokr A. Antibacterial and antibiofilm activities of polysaccharides, essential oil, and fatty oil extracted from Laurus nobilis growing in Lebanon. Asian Pac J Trop Med. 2014; 7(S1):S546-52. https://doi.org/10.1016/S1995-7645(14)60288-1

51. Kupeli E, Orhan I, Yesilada E. Evaluation of some plants used in Turkish folk medicine for their anti-inflammatory and antinociceptive activities. Pharm Biol. 2007; 45(7):547-55. https://doi.org/10.1080/13880200701498895

52. Guedouari R, Nabiev M. Anti-inflammatory activity of different extracts from Laurus nobilis growing in Algeria. Alger J Environ Sci Technol Mon Ed. Available from: www.aljest.org

53. Mukhtar DH, Begum W, Mukhtar DF. Effect of Habbul Ghar and Maul Asal in Primary Dysmenorrhea- A Randomized standard controlled clinical study. Int J Sci Res Publ. 2020; 10(7):719-20. https://doi.org/10.29322/IJSRP.10.07.2020.p10378